This project within the P01 will advance scientific understanding ofthe potential environmental etiologies of birth defects and preterm birth, which will undoubtedly have important implications for risk assessment and prevention of these common, costly, and often deadly outcomes of pregnancy. In this project we propose the following research-based aims: 1) To determine whether exposures to specific air pollutants (identified in our P20 research) are further modified by gene variants in biotransformation enzymes (e.g., NATs, GSTs, CYPH, or NOS3) for risk of selected birth defects. 2) To determine whether ambient exposures to polycyclic aromatic hydrocarbons (PAHs), during critical periods of organogenesis, are associated with women delivering infants/fetuses with birth defects, and whether relationships are further modified by gene variants in Aim 1. 3) To determine whether ambient exposures to PAHs, during critical periods of gestation, are associated with women delivering preterm, and 4) To determine whether the built environment is associated with preterm birth either directly or indirectly through a joint effect with ambient air pollution. Our proposed project is highly significant and innovative, it will be accomplished by a highly experienced group of investigators in a rigorous way, will capitalize on the intellectual capacity and resources of our existing Center (P20) as well as a new transdisciplinary research Center at Stanford devoted exclusively to studying prematurity, and will substantially move forward our scientific understanding of a specific source of environmental toxicants - air pollutants, and sentinel indicators of pediatric health - birth defects and preterm birth. No study on birth defects or spontaneous preterm birth and air pollution exposures has been done on the population scale we are proposing. This project will substantially move forward our scientific understanding of a specific source of environmental toxicants - air pollutants, and sentinel indicators of pediatric health - birth defects and preterm birth. This study's results will have obvious practical significance for women of reproductive age in the US because the study addresses individuals' risk at a very basic and potentially avoidable level, i.e., potential exposures where we live.